There are 2 clinical trials
The study will evaluate the safety, tolerability, pharmacokinetics, and anti-retroviral activity of MK-4250 monotherapy in anti-retroviral therapy (ART)-naïve, HIV-1 infected participants. The primary hypothesis of the study is that at a dose that is sufficiently safe and generally well tolerated, MK-4250 has superior antiretroviral activity compared to a historical placebo, as measured by change from baseline in plasma HIV-1 ribonucleic acid (RNA) (log10 copies/mL) at 168 hours postdose.
- No evidence at screening for mutations (e.g., E92Q, N55H, Q148K, Q148R and Y143R) affecting susceptibility to Integrase Strand Transfer Inhibitors (InSTIs) - Diagnosed with HIV-1 infection ≥ 3 months prior to screening or confirmed chronic HIV infection - Screening plasma Cluster of Differentiation (CD) 4+ T cell count of >200/mm^3 - Screening plasma HIV-1 RNA ≥5,000 copies/mL within 30 days prior to the treatment phase of this study - Anti-retroviral therapy (ART)-naïve, which is defined as having never received any antiretroviral agent OR ≤30 consecutive days of an investigational antiretroviral agent which is not an InSTI and no exposure to such an investigational antiretroviral agent within 60 days prior to screening OR ≤60 consecutive days of combination ART which does not include an InSTI and no exposure to such ART within 60 days prior to screening - Never received any InSTI - Willing to receive no other ART for the duration of the treatment phase of this study - Body Mass Index (BMI) ≤35 kg/m^2 - Other than HIV infection, have baseline health judged to be stable Exclusion Criteria: - Mentally or legally institutionalized / incapacitated, or significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder within the last 5 years - History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological (outside of HIV-1 infection), renal, respiratory, genitourinary or major neurological abnormalities or diseases - History of cancer (malignancy). --- E92Q --- --- N55H --- --- Q148K --- --- Q148R --- --- Y143R ---
Description: Plasma HIV-1 RNA will be measured. The change from Baseline in plasma HIV-1 RNA (log10 copies/mL) in participants administered MK-4250 will be compared with historical placebo data.
Measure: Plasma HIV-1 RNA Time: Day 7Description: The percentage of participants with one or more adverse events will be assessed.
Measure: Adverse Events Time: Up to Day 17Description: The percentage of participants discontinued from the study due to an adverse event will be assessed.
Measure: Study Discontinuations due to an Adverse Event Time: Up to Day 17Description: Plasma will be collected for the determination of the area under the concentration-time curve up to the last measurable concentration (AUC0-last) of MK-4250.
Measure: Area Under the Concentration-Time Curve (AUC0-last) of MK-4250 Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.Description: Plasma will be collected for the determination of the area under the concentration-time curve extrapolated to infinity (AUC0-inf) of MK-4250.
Measure: Area Under the Concentration-Time Curve (AUC0-inf) of MK-4250 Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.Description: Plasma will be collected for the determination of the area under the concentration-time curve up to 168 hours (AUC0-168) of MK-4250.
Measure: Area Under the Concentration-Time Curve (AUC0-168) of MK-4250 Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, and 168 hours after administration of MK-4250.Description: Plasma will be collected for the determination of the maximum concentration (Cmax) of MK-4250.
Measure: Maximum Concentration (Cmax) of MK-4250 Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.Description: Plasma will be collected for the determination of the concentration of MK-4250 at 168 hours postdose (C168hr).
Measure: Concentration of MK-4250 at 168 Hours (C168hr) Time: 168 hours after administration of MK-4250.Description: Plasma will be collected for the determination of the apparent terminal half-life (t1/2) of MK-4250.
Measure: Apparent Terminal Half-life (t1/2) of MK-4250 Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.Description: Plasma will be collected for the determination of the clearance (CL/F) of MK-4250.
Measure: Clearance (CL/F) of MK-4250 Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.Description: Plasma will be collected for the determination of the volume of distribution (Vz/F) of MK-4250.
Measure: Volume of Distribution (Vz/F) of MK-4250 Time: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 120, 168, and 240 hours after administration of MK-4250.The availability of antiretroviral therapy has led to a reduction in morbidity and mortality in patients with chronic HIV infection. The treatment, however, is not free of side effects, has potential interactions with other medications, is expensive and can be complex, especially in those patients who are very experienced and with mutations that give them resistance to multiple drugs. For this reason, the development of simplification strategies that avoid unnecessary exposure to antiretroviral agents remains of great interest. This is a simplification study, in which the investigators try to evaluate that with less medication the investigator can maintain the same virological control of the disease. This would mean a lower burden of medication for patients, facilitating its administration and reducing the number of unwanted side effects. Specifically, the investigators intend to evaluate the treatment with Darunavir / cobicistat plus Dolutegravir as a simplification strategy, since both drugs are taken once a day, have a powerful antiviral activity, even against antiretroviral resistant viruses, and are among the best tolerated (with fewer side effects). The results reported in some observational studies suggest that two-drug therapy (bitherapy) as a simplification strategy could also be safe and effective, however, as far as the investigators know, there are no data and clinical trials that specifically evaluate darunavir / cobicistat plus dolutegravir as a strategy of simplification.
T66I, 74M, E92Q, T97A, F121Y, E138A/K, G140A/S, Y143R/H/C, S147G, Q148H/K/R, N155H AND R263K) in historical genotyping tests. --- T66I --- --- E92Q --- --- T97A --- --- F121Y --- --- E138A --- --- G140A --- --- Y143R ---
Description: HIV-1 RNA < 50 copies/mL using a Time to Loss of Virological Response (TLOVR).
Measure: Plasma HIV-1 RNA < 50 copies/mL at 48 weeks Time: week 48Description: Percentage of patients developing ART-associated adverse events leading to treatment discontinuation.
Measure: Percentage of patients developing ART-associated adverse events Time: Since baseline to week 48Description: CD4+ cell count changes
Measure: Changes in CD4+ cell count Time: Since baseline to week 48Description: Emergence of new mutations in HIV-1 protease and integrase assessed with a genotyping test (attempted on any post Day 1 sample with HIV-1 RNA ≥ 50 copies/mL).
Measure: Emergence of new mutations in HIV-1 protease and integrase Time: Baseline and in case of virological failure, defined as ≥ 50 copies/mL in 2 consecutive determinations or a single HIV-1 RNA values > 1000 copies/mL. We can observe a virological failure throughout the study (from baseline to week 48)Description: HIV-1 RNA< 50 copies/mL at 24 weeks by TLOVR
Measure: Plasma HIV-1 RNA < 50 copies/mL at 24 weeks Time: Week 24Description: HIV-1 RNA < 50 copies/mL at 24 and 48 weeks using the FDA snapshot analysis (sensitivity analysis).
Measure: Plasma HIV-1 RNA < 50 copies/mL at 24 and 48 weeks Time: Week 24 and 48Description: Description of plasmatic trough levels of DTG and DRV/cobi in the experimental group, and in those patients experiencing virological failure.
Measure: DTG and DRV/cobi plasma concentration Time: Week 4Description: ART prices
Measure: Cost associated with the antirretroviral treatment of the study Time: Since baseline to week 48Description: Prices of clinical controls during the study
Measure: Estimated costs of clinical controls Time: Since baseline to week 48